Optimizing First-Line Chemotherapy in Metastatic Pancreatic Cancer: Efficacy of FOLFIRINOX versus Nab-Paclitaxel Plus Gemcitabine

SIMPLE SUMMARY: Metastatic PC often represents a complex decision-making moment for oncologists, particularly due to the general conditions of the patients, age, and the potential toxicity of chemotherapy. Choosing the best first-line treatment is the first step towards improving survival and quality of life. In this review, the authors discuss the most accredited strategies today and the predictable toxicities, as well as clinical factors (age, PS, etc.). ABSTRACT: Pancreatic cancer (PC) is one of the most lethal tumors in Europe with an overall 5-year survival rate of 5%. Since 1992, gemcitabine (Gem) has been the treatment of choice for metastatic disease with significant improvement in median overall survival (OS) compared to fluorouracil. A good performance status (PS) at diagnosis appears to be a strong predictive factor for better survival. Overall, 50% of PC are metastatic or locally advanced at diagnosis, and more than 70% of the resected patients will experience a recurrence, with a median OS ranging from 4 to 10 months (mos). FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and Nab-paclitaxel (Nab-p) plus Gem have recently increased survival of patients with metastatic PC, over Gem. Treatment with FOLFIRINOX is generally considered more effective with respect to the doublet, with toxicity concerns, FOLFIRINOX achieves an overall response rate (ORR) of 31.6%, while for Nab-p plus Gem ORR is 23%; however, FOLFIRINOX was associated with higher rates of grade 3 and higher adverse events. Although the international guidelines indicate that both regimens can be used as first-line therapy for patients with metastatic PC, FOLFIRINOX is the most widely used; Nab-p plus Gem is more frequently used in patients with lower PS. In this review, we critically analyze these two regimens to give a pragmatic guide to treatment options.